SAT-222 Hormone Responses Associated with Letrozole Ovulation Induction in Anovulatory Women with PCOS

Abstract: The aromatase inhibitor (AI) letrozole has been shown to be the most effective oral medication for ovulation induction in anovulatory women with PCOS. It has been established that AIs block the conversion of androgens to estrogen, leading to reduction of serum estrogen levels. However, the mechanism by which letrozole induces ovulation is unknown. It has been suggested that the mechanism of AIs in ovulation induction may involve increased FSH secretion in response to reduced estrogen levels. To examine the mechanism by which AIs induce ovulation, we performed a pilot interventional study. Ten anovulatory women with PCOS, aged 24-34 years were enrolled. Each subject underwent baseline serum hormone assessment and transvaginal ultrasound. Women were excluded if they had hypogonadotropic hypogonadism, or ultrasound evidence of a dominant follicle or corpus luteum. Each subject underwent ovulation induction with letrozole 2.5 mg/day for 5 days. Repeat transvaginal ultrasound was done three days after completing letrozole. Ovulation was defined by (1) presence of >=1 ovarian follicle >=16 mm on follow up ultrasound and (2) positive home ovulation predictor test. Serum hormone levels were assessed in all subjects at baseline and at two, four, and seven days after letrozole initiation. Mean serum hormone levels were compared using paired Student’s t test with statistical significance set at p<0.05. Three of 10 subjects ovulated after completing letrozole. In all subjects, the baseline levels (mean ± SD) of serum FSH, LH, estradiol, and androstenedione were 5.4 ± 2.2 mIU/mL, 12.1 mIU/mL, 86.2 ± 32.1pg/mL, and 3.2 ± 1.5 ng/mL, respectively. A significant reduction in serum estradiol was noted on day two compared to baseline (-35.2 pg/mL). There was a significant increase in mean serum FSH (+1.8 mIU/mL) and LH (+4.7 mIU/mL) on day two after starting letrozole. Significant increases in serum androstenedione were observed on day two (+0.8 ng/mL) and day four (+1.5 ng/mL) relative to baseline values. The study was not sufficiently powered to detect differences in serum hormone levels between women that did and did not ovulate in response to letrozole administration. These data suggest that the mechanism of ovulation induction by AI may involve a transient increase in serum gonadotropins resulting from interrupted estrogen negative feedback. Sources of Research Support: NIH Grants T32 HD007203, K12 HD001259, and P50 HD012303.Key Words: Polycystic Ovary Syndrome; Infertility; Anovulation